OBJECTIVES: This study aimed to test the association between of type and number of D'Amico high-risk criteria (DHRCs) with cancer-specific mortality (CSM) in high-risk prostate cancer patients treated with radical prostatectomy. MATERIALS AND METHODS: In the Surveillance, Epidemiology, and End Results database (2004-2016), we identified 31,281 radical prostatectomy patients with at least 1 DHRC, namely, prostate-specific antigen (PSA) >20 ng/mL (hrPSA), biopsy Gleason Grade Group (hrGGG) score of 4 and 5, or clinical tumor stage ≥T3 (hrcT). Multivariable Cox regression models and competing risks regression models (adjusting for other cause mortality) tested the association between DHRCs and 5-year CSM. RESULTS: Of 31,281 patients, 14,394 (67%) exclusively harbored hrGGG, 3189 (15%) harbored hrPSA, and 1781 (8.2%) harbored hrcT. Only 2132 patients (6.8%) harbored a combination of the 2 DHRCs, and 138 (0.6%) had all 3 DHRCs. Five-year CSM rates ranged from 0.9% to 3.0% when any individual DHRC was present (hrcT, hrPSA, and hrGGG, in that order), 1.6% to 5.9% when 2 DHRCs were present (hrPSA-hrcT, hrcT-hrGGG, and hrPSA-hrGGG, in that order), and 8.1% when all 3 DHRCs were present. Cox regression models and competing risks regression confirmed the independent predictor status of DHRCs for 5-year CSM that was observed in univariable analyses, with hazard ratios from 1.00 to 2.83 for 1 DHRC, 2.35 to 5.88 for combinations of 2 DHRCs, and 7.13 for all 3 DHRCs. CONCLUSIONS: Within individual DHRCs, hrcT and hrPSA exhibited weaker effects than hrGGG did. Moreover, a dose-response effect was identified according to the number of DHRCs. Accordingly, the type and number of DHRCs allow further risk stratification within the high-risk subgroup.

Cancer Prognostics and Health Outcomes Unit Division of Urology University of Montréal Health Center Montréal Québec Canada

Department of Maternal Child and Urological Sciences Sapienza Rome University Policlinico Umberto 1 Hospital Rome Italy

Department of Surgical and Diagnostic Integrated Sciences University of Genova Genova Italy

Department of Urology 2nd Faculty of Medicine Charles University Prague Czech Republic

Department of Urology Comprehensive Cancer Center Medical University of Vienna Vienna Austria

Department of Urology IRCCS Policlinico San Martino Genova Italy

Department of Urology University Hospital Frankfurt Frankfurt am Main Germany

Department of Urology University of Texas Southwestern Dallas TX USA

Department of Urology University of Verona Azienda Ospedaliera Universitaria Integrata di Verona Verona Italy

Department of Urology Weill Cornell Medical College New York NY USA

Division of Experimental Oncology Unit of Urology URI Urological Research Institute IRCCS San Raffaele Scientific Institute Milan Italy

Division of Urology Department of Special Surgery Jordan University Hospital The University of Jordan Amman Jordan

Institute for Urology and Reproductive Health 1 M Sechenov 1st Moscow State Medical University Moscow Russia

IRCCS Ospedale Policlinico San Martino Genova Italy

Martini Klinik Prostate Cancer Center University Hospital Hamburg Eppendorf Hamburg Germany

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